title: Growth failure, encephalopathy, and endocrine dysfunctions in two siblings, one with 5-oxoprolinase deficiency.
abstract: Two female siblings, born to consanguineous parents, presented with a similar phenotype characterized by severe growth and developmental failure, dysmorphic features, thyroid and gonadal dysfunction, autistic traits and hand stereotypes resembling Rett syndrome. In the elder patient, analysis of urinary organic acids disclosed a very high excretion of 5-oxoproline (4.2 to 8.1 mol/mol creatinine) and enzyme assays of leucocyte extracts revealed a profound deficiency of 5-oxoprolinase. However, normal urinary organic acid profiles were found in the younger child. In view of their distinct dysmorphic features and severe growth deficiency, these siblings cannot be considered as Rett Syndrome variants. The Dubowitz and carbohydrate-deficient glycoprotein syndromes were also excluded clinically and biochemically respectively. We conclude that these patients suffer from a hitherto undescribed autosomal recessive disorder, unrelated to the 5-oxoprolinase deficiency of the elder sib.
  
  
  CONCLUSIONS
  The present findings give evidence that 5-oxoprolinase deficiency is not associated with a distinct morbid phenotype.
authors.affiliation: Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
authors.forename: L H
authors.initials: LH
authors.lastname: Cohen
authors.forename: E
authors.initials: E
authors.lastname: Vamos
authors.forename: C
authors.initials: C
authors.lastname: Heinrichs
authors.forename: M
authors.initials: M
authors.lastname: Toppet
authors.forename: W
authors.initials: W
authors.lastname: Courtens
authors.forename: A
authors.initials: A
authors.lastname: Kumps
authors.forename: Y
authors.initials: Y
authors.lastname: Mardens
authors.forename: B
authors.initials: B
authors.lastname: Carlsson
authors.forename: L
authors.initials: L
authors.lastname: Grillner
authors.forename: A
authors.initials: A
authors.lastname: Larsson
mesh_terms: D001927:Brain Diseases / Q000201:enzymology / Q000235:genetics; D003241:Consanguinity; D004700:Endocrine System Diseases / Q000201:enzymology / Q000235:genetics; D005260:Female; D006130:Growth Disorders / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007223:Infant; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D011752:Pyroglutamate Hydrolase / Q000172:deficiency*; D013577:Syndrome
chemical_list: D011752:Pyroglutamate Hydrolase